2ace



ACETYLCHOLINESTERASE (E.C. 3.1.1.7) FROM TORPEDO CALIFORNICA (see also AChE inhibitors and substrates)



Overview
Solution of the three-dimensional (3D) structure of Torpedo californica acetylcholinesterase (TcAChE) in 1991 (Sussman et al. & Silman (1991)) opened up new horizons in research on an enzyme that had already been the subject of intensive investigation. The unanticipated structure of this extremely rapid enzyme, in which the active site was found to be buried at the bottom of a deep and narrow gorge, lined by 14 aromatic residues (colored darkmagenta) , led to a revision of the views then held concerning substrate traffic, recognition, and hydrolysis (Botti et al. Sussman & Silman (1999)). This led to a series of theoretical and experimental studies, which took advantage of recent advances in theoretical techniques for treatment of proteins, such as molecular dynamics and electrostatics and to site-directed mutagenesis, utilizing suitable expression systems. Acetylcholinesterase hydrolysizes the neurotransmitter acetylcholine (ACh), producing choline and an acetate group. ACh directly binds Ser200 (via its nucleophilic Oγ atom) within the catalytic triad (Ser200, His440, and Glu327). The residues Trp84 and Phe330 are also important in the ligand recognition. After this binding acetylcholinesterase hydrolysizes ACh.

About this Structure
2ACE is a Single protein structure of sequence from Torpedo californica with ACH as ligand. This structure superseeds the now removed PDB entry 1ACE. Active as Acetylcholinesterase, with EC number 3.1.1.7 Structure known Active Site: CAT. Full crystallographic information is available from OCA.

Additional Resources
For additional information, see: Alzheimer's Disease

Reference
Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A., Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL, Nat Struct Biol. 1997 Jan;4(1):57-63. PMID:8989325

Page seeded by OCA on Thu Nov 8 12:46:15 2007